Field of the Invention
The invention relates to materials suitable for use in a variety of medical devices, particularly in medical devices adapted to carry or contact blood, including devices implanted or temporally used in the body and devices that carry or contact blood extracorporeally.
Discussion of the Related Art
A variety of devices are used to convey blood or otherwise make contact with blood in both mammalian bodies and extracorporeally. Such devices include vascular grafts, stents and stent-grafts and other endoluminal devices, catheters, vascular patches, defect closure devices, blood tubing, etc. Generally, all of these devices must perform their designated functions without engendering unwanted blood clot formation, accumulation of occlusive materials, or other adverse reaction from the blood vessel or various blood components.
Some researchers believed it desirable for certain implantable medical devices, such as vascular grafts, to be both porous enough to allow certain blood components to attach to and grow into the devices but not so porous that blood and/or serum will leak through the device. For example, U.S. Pat. No. 6,436,135 to Goldfarb describes an expanded polytetrafluoroethylene (ePTFE) graft with a microstructure of nodes and fibrils and specific wall thicknesses where “ . . . the average internodular distance [of a vascular graft], as measured along the axis of expansion 12, must fall within a relatively narrow range of values, viz., between approximately 6 and 80 microns.” Col. 5, lines 31-34. The patent states that: “Where the average internodular distance is less than the major dimension of a typical red cell, or approximately 6 microns, inadequate cellular ingrowth has been observed. In such cases, the node/fibril superstructure is so tightly packed as to preclude either the establishment or continued nutrition of a viable neointima.” Col. 5, lines 48-53.
The Goldfarb patent characterizes particular parameters required to provide a suitable surgically implanted vascular graft as follows: “ . . . a prosthetic vascular device formed from a small bore tube of polytetrafluoroethylene which has been heated, expanded and sintered so as to have a microscopic superstructure of uniformly distributed nodes interconnected by fibrils and characterized by: (a) an average internodular distance which is (i) large enough to allow transmural migration of typical red cells and fibroblast [sic], and (ii) small enough to inhibit both transmural blood flow at normal pressures and excessive tissue ingrowth; and (b) an average wall thickness which is (i) small enough to provide proper mechanical conformity to adjacent cardiovascular structures, and (ii) large enough, when taken in conjunction with the associated internodular distance, to prevent leakage and excess tissue ingrowth, to allow free and uniform transmilral [sic] nutrient flow, and to assure mechanical strength and ease of implantation.” Col. 3, lines 40-55.
Other researchers suggest that these theories of blood behavior described in the Goldfarb patent, particularly as applied to humans, may be incorrect. For example, U.S. Pat. No. 6,517,571 to Brauker et al., taught that the performance of a vascular graft or stent-graft could be improved by providing an extremely smooth blood contact surface. Brauker et al. recommend employing a base graft with an internodal distance between 5 to 90 micron, but then applying to that base tube a very smooth film to provide a luminal surface that resists or prevents adhesion of occlusive blood components. See, e.g., Col. 4, lines 18-24; col. 6, lines 1-5. Brauker et al. assert: “The surface smoothness is believed to avoid or reduce adherence of occlusive blood components including blood platelets which are typically of about 2-4 micron diameter. The small pore size (generally characterized as the mean fibril length of the ePTFE microstructure) is preferably less than about 5 microns and more preferably less than about 3 microns. It is believed that the fibril length or pore size may be reduced until the smooth surface is non-porous, substantially non-porous or even entirely non-porous.” Col. 4, lines 47-55.
Brauker et al. define “smoothness” as follows: “The parameter of concern for smoothness of the luminal surface (surface values) of the present invention is Rq, which is the Root-Mean-Square roughness, defined as the geometric average of the roughness profile from the mean line measured in the sampling length, expressed in units of microns RMS. The luminal surface (i.e., the blood contacting surface) of the vascular graft of the present invention has a surface at least as smooth as about 1.80 microns RMS . . . ” Col. 4, lines 25-33.
By providing this exceptionally smooth blood contact (luminal) surface, Brauker et al. seek to avoid accumulation of occlusive elements while still maintaining vascular graft function. The patent states: “This luminal surface lining is intended to provide a smooth surface to the vascular graft which is believed to be substantially non-adherent to occlusive blood components such as platelets, fibrin and thrombin, and impermeable to cells from the blood, thereby avoiding the formation of an occlusive coating which might ultimately increase in thickness over time and eventually result in graft occlusion. These increasingly thick coatings are known to be particularly problematic at the distal anastomoses of vascular grafts wherein it has been frequently documented that intimal hyperplasia occurring at that location will lead to occlusion and loss of graft patency. While these occlusive blood components are substantially prevented from sticking to the surface of the inventive graft, it is believed that various other blood components such as, for example, various proteins and/or endothelial cells, may still adhere to the surface without leading to a coating of the occlusive blood components responsible for a thickening neointima over time.” Col. 4, line 64, to col. 5, line 15.
While the Brauker et al. patent provides significant improvements in implantable blood contact device performance, we have found that much better blood-vessel-device interaction can be achieved by significantly modifying the microstructure of the blood contact surface.